N-acetylneuraminate lyase (NANL), also known as N-acetylneuraminate aldolase, and acylneuraminate-pyruvate lyase, is an enzyme that catalyzes the conversion of N-acetylneuraminic acid (sialic acid) into pyruvate and N-acetyl-D-mannosamine, as well as the reverse reaction. In bacteria, NANL is involved in energy metabolism, and the degradation of sialic acid produces usable carbon and energy sources for the bacteria. The expression and activity of NANL in bacteria are regulated by the level of sialic acid. (Vimr, E. R. and Troy, F. A. (1985) J. Bacteriol. 164:854-860.) NANL has been described in a number of mammalian tissues where it is a key enzyme in sialic acid metabolism.
Sialic acid is an essential constituent of a class of glycolipids known as gangliosides. Gangliosides are composed of a lipid component, ceramide, and an oligosaccharide component. The oligosaccharide component always includes sialic acid and may contain other sugars such as glucose, galactose, and N-acetylgalactosamine. Gangliosides were first described in neural tissue, particularly in grey matter, but have since been shown to exist in nearly all tissues. Gangliosides are components of the cell membrane, and they act as receptors for a variety of molecules and participate in cell-to-cell interactions and in signal transduction. Gangliosides are also found in the membranes of intracellular organelles, such as secretory granules, where their roles are less well-defined. Defects in ganglioside expression are important in some disease processes including two forms of storage defects, GM.sub.2 gangliosidosis, Tay-Sachs/.beta.-hexosaminidase deficiency, and GM, gangliosidosis, .beta.-galactosidase deficiency. The accumulation of gangliosides in the lysosomes of neurons is characteristic of these diseases. In addition auto-antibodies to gangliosides have been demonstrated in a number of autoimmune disorders including multiple sclerosis, lupus erythematosus, and type I diabetes mellitus. Thus, aberrations in sialic acid metabolism and NANL are involved in autoimmune disorders. (Meysick, K. C. et al. (1996) Mol. Biochem. Parasitol. 76:289-292; Misasi, R. et al. (1997) Diabetes Metab. Rev. 13:163-179).
The discovery of a new human N-acetylneuraminate lyase and the polynucleotides encoding it satisfies a need in the art by providing new compositions which are useful in the diagnosis, treatment, and prevention of cancer and autoimmune disorders.